134430-45-8

Upstream product

• 100-46-9 benzylamine 
• 54505-72-5 diethylmalonyl chloride 
• 27132-23-6 diethylmalonic acid dimethyl ester 
• 77-25-8 diethyl diethylmalonate 
• 57-44-3 diethylbarbituric acid 
• 83356-06-3 5,5-diethyl-1,3-diphenylmethyl-2,3,4(1H,3H,5H)pyrimidinetrione 

Relevant academic research and scientific papers

Azetidine-2,4-diones (4-oxo-β-lactams) as scaffolds for designing elastase inhibitors

A new class of inhibitors 4-oxo-β-lactams (azetidine-2,4-diones), containing the required structural elements for molecular recognition, inhibit porcine pancreatic elastase (PPE) but show a dramatically lower reactivity toward hydroxide compared with the analogous inhibitors 3-oxo-β-sultams. Inhibition is the result of acylation of the active site serine and electron-withdrawing substituents at the N-(4-aryl) position in 3,3-diethyl-N-aryl derivatives increasing the rate of enzyme acylation and generating a Hammett ρ-value of 0.65. Compared with a ρ-value of 0.96 for the rates of alkaline hydrolysis of the same series, this is indicative of an earlier transition state for the enzyme-catalyzed reaction. Docking studies indicate favorable noncovalent interactions of the inhibitor with the enzyme. Compound 2i, the most potent inhibitor against PPE, emerged as a very potent HLE inhibitor, with a second-order rate for enzyme inactivation of ～5 × 105 M-1 s-1.

Decarbonylation of tetrasubstituted barbituric acids as a versatile method for preparation of N,N',2,2-tetrasubstituted malonamides

A procedure for the preparation of 1,3,5,5-tetrasubstituted- 2,3,4(1H,3H,5H)pyrimidinetriones (barbituric acids) through alkylation of the less substituted 2,3,4(1H,3H,5H)pyrimidinetriones (barbituric acids) and decarbonylation of the tetrasubstituted product into the N,N,2,2- tetrasubstituted-manlonamides are described. (C) 2000 Elsevier Science Ltd.